In a study reported in the Journal of Clinical Oncology by Chapuis et al, concurrent use of cytotoxic T lymphocyte (CTL) antigen-4 (CTLA-4) blockade with ipilimumab (Yervoy) and adoptively transferred antigen-specific CTLs produced enduring responses in patients with stage IV melanoma. Cassian Yee, MD, of MD Anderson Cancer Center, is the corresponding author of the article.
In the study, autologous MART1 (melanoma antigen)-specific CTLs were generated by priming with peptide-pulsed dendritic cells in the presence of interleukin-21 and enriched by peptide-MHC multimer-guided cell sorting. A total of 10 patients received the MART1-specific CTLs followed by a standard course of ipilimumab.
At 12-week evaluation, 2 patients had complete remission, 1 had partial response on RECIST (Response Evaluation Criteria in Solid Tumors; 2 on immune-related response criteria), and 3 had stable disease. Infused CTLs persisted at a frequency of up to 2.9% of CD8+ T cells for the duration of monitoring, including up to 40 weeks. In patients with complete remission, partial response, or stable disease, persisting CTLs exhibited phenotypic and functional characteristics of long-lived memory T cells, and these patients were observed to exhibit responses to nontargeted tumor antigens.
At a median follow-up of 187 weeks, 5 patients remained alive and 2 remained in complete remission. The toxicity profile of the combined treatment was similar to that seen with ipilimumab alone.
The investigators concluded:
We demonstrate that combining antigen-specific CTLs with CTLA-4 blockade is safe and produces durable clinical responses, likely reflecting both enhanced activity of transferred cells and improved recruitment of new responses, highlighting the promise of this strategy. ■
Chapuis AG, et al: J Clin Oncol. June 6, 2016 (early release online).